Hamburger, Viktor

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(b. Landeshut, Silesia [later Poland], 9 July 1900; d. St. Louis, Missouri, 12 June 2001),

embryology, neuroembryology.

Hamburger was one of the most influential neuroembryologists of the twentieth century. A student of Hans Spemann at Frieburg, he was among the first to transfer to the chick embryo the transplantation techniques worked out in Spemann’s lab on amphibians. During the early part of his career, he studied the problem of how the vertebrate limb is innervated during embryonic development. This work, carried out from the late 1940s onward in partial collaboration with Rita Levi-Montalcini, led to discovery of nerve growth factor (NGF), a protein that maintains nerve cells as they grow out from the central nervous system to a peripheral target such as a limb bud. For isolating and characterizing NGF Levi-Montalcini and the biochemist Stanley Cohen received the 1976 Nobel Prize in Medicine or Physiology. For the last thirty years of his career Hamburger studied the neurological basis of endogenous pre-hatching behavior patterns in the chick. He also maintained a continuing interest in the history of his field, authoring numerous articles over the course of fifty years and one book, The Heritage of Experimental Embryology (1988).

Hamburger was one of two sons born to Max and Else Hamburger, who had moved from Breslau (later Wroclaw, Poland) to take over the family textile industry. Max Hamburger was considered a progressive in his day, establishing one of the first organized and planned residential towns (not a “company town” in the U.S. sense) in eastern Europe for workers in his factory. Hamburger’s parents were middle-class and well-educated: His father was an avid art collector and friend of many important German artists and his mother an ardent naturalist. Hamburger often said that his mother introduced him to a love of nature, and his father to a love of art. Later in life Hamburger became a modest collector of art himself, and one of his favorite outings was to visit the St. Louis Art Museum; the other was to go on field trips with his colleagues from the Biology Department at Washington University. Although he was primarily a laboratory biologist, field trips into natural areas always remained one of his most satisfying activities.

Hamburger attended the universities of Breslau, Heidelberg, Munich, and Freiburg, obtaining his PhD at the latter in 1925 under the direction of Hans Spemann. He served as a research associate at the University of Göttingen (1925–1926) and at the Kaiser-Wilhelm Institute for Biology in Berlin-Dahlem (1926–1927). In 1927 he returned to Freiburg for five years (1927–1932), when he was awarded a Rockefeller fellowship at the University of Chicago. While he was in Chicago, the National Socialist government came to power in Germany, and Hamburger was dismissed from his post. He remained in Chicago two more years, finally accepting a post as assistant professor of zoology at Washington University in St. Louis, Missouri, where he remained for the rest of his life. He retired officially in 1966, but continued his laboratory work for another twenty years.

In 1928 Hamburger married Martha Fricke, a young biologist whom he had met in Göttingen. They had two daughters, Doris (born in Germany) and Carola (born in the United States). In his scientific and personal life Hamburger was known for his quiet, almost self-effacing manner, his incisive views and his dry wit. He worked intensively and with great concentration, always a hands-on experimentalist, continuing laboratory work into his mid-eighties. Although always well-funded (Rockefeller Institute, NIH), and a nurturing mentor to graduate students and post-docs, he never became a scientific entrepreneur. He accepted only as many people in his laboratory as he could work with directly, and he never lost day-to-day contact with his first love, the embryos, the frog and later the chick.

Background and Education . Hamburger’s interest in nature began with early childhood hikes into the mountains and fields around Landeshut and at the family’s summer home in the mountains near the Bohemian border, where he often collected frog and salamander eggs that he watched develop to tadpoles and then metamorphose into adults in an aquarium at home. After graduating from gymnasium (secondary school) in June, 1918, Hamburger was inducted into the German army and sent to basic training in Breslau. Had the armistice not been signed in early November, he would undoubtedly have been sent to the front. After being discharged, he remained in Breslau where he took several courses at the university—in zoology, botany, geology and mathematics—while trying to decide how he might pursue a career in science. The turbulent social and economic conditions in Germany immediately after the war did not make such decisions easier. His parents suggested he should get some experience beyond the confines of Silesia. As it happened, his father’s first cousin, Clara Hamburger, was assistant to the distinguished protozoologist Otto Bütschli at the University of Heidelberg. So for the academic year 1919–1920 he enrolled as a full-time student. In addition to a philosophy seminar taught by Hans Driesch, the other course that made a considerable impression was a graduate seminar on developmental biology taught by Curt Herbst, Driesch’s long-time collaborator from their years together at the Naples Zoological Station. It was in Herbst’s seminar that he first had contact with the work of Wilhelm Roux, which stirred his imagination. Reporting on the seminar years later, Hamburger wrote: “It was that seminar that decided my fate—I was to become an experimental embryologist” (Hamburger, 1988, p. 16). However, the sort of experimental embryology that Herbst himself pursued—physiological studies of the effects of calcium, lithium and other ions on patterns of development— seemed to Hamburger to be too chemical and reductionist. He looked for other possibilities.

The Spemann Laboratory at Freiburg . In the spring of 1920 Hamburger and a friend visited the Black Forest area near Freiburg on a short holiday. He liked the prospects for hiking and skiing in the mountains nearby, and so when he learned from Clara Hamburger that a distinguished zoologist, Hans Spemann, headed the Zoological Institute there Hamburger applied, and was accepted by Spemann as a graduate student at the Institute for the fall of 1920.

The atmosphere at Freiburg was open and relaxed. Students determined their own course of study, which was highly varied and almost wholly self-directed. Most of his time the first year was spent in the grosse Praktikum, an allday laboratory course, in which individual students studied, at their own tempo, representatives of all phyla, from protozoa to mammals, using preserved specimens and microscope slides. It was in Spemann’s Institute that Hamburger met what were to become his two closest friends, Johannes Holtfreter and Hilde Proescholdt, who was just then starting her groundbreaking work on transplantation of tissue from the dorsal “lip” of the blastopore (the area of pushing inward of cells in the gastrula stage of embryonic development), that eventually led to the concept of the “Organizer” and Spemann’s 1935 Nobel Prize. The laboratory was an exciting and stimulating place. Discussions occurred daily among the students about their own work and every other conceivable subject, from philosophy of art to politics, literature, and of course, science. Holtfreter was to remain a friend and colleague for life. Proescholdt (soon to be married to Otto Mangold) died several years later.

For his PhD dissertation, completed in the spring of 1925, Hamburger undertook to study the role of the nervous system in the development of peripheral organs such as the limbs (using the frog, Rana fusca). Earlier work had suggested that ablation of developing eye tissue had resulted in, among others, defects in limb development. In repeating the earlier experiments, Hamburger found no clear relationship between eye and leg development. However, his experiments did suggest a novel idea: innervation was not necessary for normal limb bud differentiation (though it was necessary for later functional development of the limbs). He established this principle unambiguously later, while working at the Kaiser-Wilhelm Institute for Biology in Berlin-Dahlem.

After Freiburg, Hamburger spent several months working at the Stazione Zoologica in Naples before taking up a postdoctoral position in Göttingen with Alfred Kühn, whom Hamburger described as a polymath and the “universal genius among German zoologists” (1988, p. 101). Kühn assigned Hamburger to one of his many ongoing projects, studying color vision in fish, The project never got very far but the stay in Göttingen did help Hamburger establish a number of contacts among leading German biologists who passed through Kühn’s laboratory. It was also in Göttingen that he met his future wife, Martha Fricke.

Moving from Göttingen to the Mangold laboratory at the Kaiser-Wilhelm Institute for Biology in 1926, Hamburger found himself in the center of much new, exciting work, especially in the area of developmental genetics. The embryology department was on the first floor of the institute building, while Richard Gold-schmidt’s genetics department was on the floor above. Hamburger regularly attended the afternoon teas with the genetics group, where he became close friends with Curt Stern, later to become one of the twentieth century’s leading geneticists. Goldschmidt fostered a strong interest within his group in the relationship between genetics and development, a connection that had been largely ignored in Spemann’s laboratory. Although Hamburger’s attempt in collaboration with Stern to carry out some breeding experiments with the fruit fly, Drosophila, did not yield any useful results, the relationship between genetics and embryology that this work inspired became a guiding principle for his later work on interspecific crosses among species of salamanders, which involved observing changes in developmental timing (similar to Goldschmidt’s work on interspecific crosses in the gypsy moth, Lymantria). After arriving in the United States, he also studied the developmental genetics of a mutation in chickens known as “creeper” because they have developmental problems of the limbs that produce creeping-like motion (Hamburger, 1941, 1942).

From Freiburg to Chicago . When Hamburger was recalled by Spemann to Freiburg in 1927 to become a privatdozent, his main teaching assignment was the grosse Prakticum. He succeeded in establishing an atmosphere of excitement among the laboratory students with his constant questioning and discussion of major developments in the field, especially experimental embryology and genetics. Hamburger’s position, and eventually ascendancy through the ranks at Freiburg, seemed assured. In 1932 the Rockefeller Foundation invited Spemann to nominate a candidate for a one-year postdoctoral fellowship to the United States (specifically to the laboratory of Frank Rattray Lillie in Chicago). Spemann at first wanted to nominate Otto Mangold, but he was over the age limit of thirty-five stipulated by the foundation, so Spemann nominated Hamburger instead. The main aim was to adapt the methods and techniques of experimental transplantation developed for amphibians in the Freiburg lab to work on chick embryos in Chicago. Leaving his family

(with a newborn daughter) in Germany, Hamburger came to the Lillie lab in the fall of 1932.

The initial problem on which Hamburger focused grew out of conflicting results obtained in 1909 by one of Lillie’s students (Elizabeth Shorey) using the chick, and a decade later (1919) those of one of Ross Harrison’s graduate students (Sam Detwiler) at Yale. The question related to the effects of damaging or removing developing chick limb buds on the further development of sensory and motor nerve tracts in the spinal cord. Shorey, using electrocautery, noticed hypoplasia (diminished development) of both motor and sensory nerve columns. By contrast, Detwiler, using limb extirpation and transplantation methods, found that extirpation caused hypoplasia only in sensory nerve columns, and that transplantation of limb buds to other areas of the embryo resulted in hyperplasia primarily of sensory nerve ganglia. Lillie suggested that Hamburger reinvestigate the problem, using the Spemann techniques of microsurgery on the chick, to resolve the discrepancy.

Hamburger learned microsurgical methods for chick embryos from others in the lab, applying the glass needle end hair-loop techniques developed in Freiburg for limb bud extirpation to determine the effects of development of the adjacent nervous system. The results were clear: Shorey’s observation that both sensory and motor neurons responded to extirpation with hypoplasia, was confirmed. In addition to the actual results, Hamburger was immediately impressed with the use of the chick as a model for investigating vertebrate development. In contrast to amphibians, where motor neurons are not organized into the easily-observed motor columns, in the chick embryo, the motor columns are clearly visible, and thus provide favorable material for analyzing changes in their numbers and size in a way that the amphibian embryo does not allow. From this point onward the chick became Hamburger’s primary model organism.

In the middle of his year in Chicago, the National Socialist government came to power in Germany, and within months had promulgated the “Law for the Restoration of the Professional Civil Service,” removing all civil servants (which included university employees) of Jewish descent from their jobs. Hamburger was dismissed from his post at Freiburg, and Spemann was powerless to alter the decision. With an extension of the Rockefeller grant Hamburger was able to remain in Chicago until 1935. Returning briefly to Germany to bring his family to the United States, he began searching for jobs. There were only three prospects: Odessa (USSR), Sao Paulo (Brazil) and Swarthmore College. He had decided that the best opportunities for research lay in the United States, but Swarthmore was a small liberal arts college where he would have a heavy teaching load. Fortuitously, a position opened up in 1935 at Washington University, and Hamburger jumped at the opportunity. At Washington he advanced from assistant professor (1935–1939), associate professor (1939–1941), and full professor (1941–1966), and after retirement in 1966, he was appointed Edward Malinckrodt Distinguished University Professor (1968) taking emeritus status in 1969. He served as department chairman for twenty-six years (1941–1966).

The vast bulk of Hamburger’s research work from 1935 onward focused on three major areas in chick development: (1) the relationship between limb bud extirpation (and reimplantation) and its effects on the outgrowth of motor columns in the spinal cord; (2) developmental genetics of the creeper fowl mutation; and (3) the development of chick behavior, especially during the pre-hatching period.

One of the outcomes of Hamburger’s early extirpation work in Chicago was the accidental discovery (based upon his unconscious removal of different amount of limb bud tissue) that there appeared to be a quantitative relationship between the amount of limb bud tissue removed and the degree of hypoplasia in the lateral motor

columns and the related sensory neurons. He also noted that when he transplanted limb bud tissue to other regions of the embryo (flank or belly) that hyperplasia of the motor neurons was enhanced.

In a paper of 1934 Hamburger interpreted this work in the framework of Spemann’s induction theory, by putting forward three major conceptual points: (1) The developing peripheral tissue (in this care limb bud) stimulates (by way of an inducer substance) the growth of neurons toward the developing tissue; (2) The inducer substance is transported by retrograde movement from the growing neuron tip back to the cell body to stimulate further growth; and (3) The effect is quantitative: the greater the quantity of inducing tissue, the greater the rate of neuronal growth (and vice-versa, with removal of limb bud tissue).

Discovery of Nerve Growth Factor (NGF) . Hamburger had sent a copy of his 1934 paper to an eminent colleague, Giuseppe Levi at the University of Turin Medical Faculty, who eventually passed it on to one of his young post-docs, Rita Levi-Montalcini. During the war, working in exile in the Italian countryside, Levi-Montalcini (who was also Jewish and dismissed from her position in Turin) was intrigued with this paper and had repeated Hamburger’s experiments. Publishing her results, along with those of several other Italian workers after the war, Levi-Montalcini came up with a very different interpretation. She had noted something Hamburger had not: After an initial period of proliferation and growth in the non-extirpated side of the chick spinal cord a certain percentage of cells in the motor ganglia began to degenerate, a process she called neuronal death. This was apparently normal, leading Levi-Montalcini to postulate that the limb bud does not have an inductive capacity, but provides a “maintenance factor” that prevents massive neuronal death. When Hamburger read Levi-Montalcini’s papers after the war, he was impressed with her work and immediately invited her to St. Louis to work in his lab and try to resolve the discrepancies. With funds provided by the Rockefeller Foundation, Levi-Montalcini came to St. Louis in 1947 for what was intended to be a one-year period. As the work proceeded with exciting results, Hamburger arranged for an extension of the Rockefeller funds, and eventually procured for Levi-Montalcini a faculty position at Washington University that she held for the next thirty years.

In repeating Hamburger’s experiments, Levi-Montalcini pointed out the general feature of neuronal death that Hamburger had missed, confirming the hypothesis that the limb bud produces a maintenance rather than an inducing factor. The obvious next step was to isolate and identify the chemical agent responsible, but that was difficult working with chick limb bud tissue, which exists in very small quantities. As it happened, in 1948 Hamburger received a paper from a former student, Elmer Bueker (then at Georgetown University Medical School), detailing an experiment in which he had transplanted a mouse sarcoma into a developing chick egg. Shortly afterward, he noted that the tumor had been thickly invaded by sensory neurons, suggesting that the tumor produced some sort of neuron-stimulating factor.

With Bueker’s permission, Hamburger and Levi-Montalcini repeated the experiment and observed a clear quantitative relationship between size of sarcoma and neuronal growth rate. Not being biochemically knowledgeable himself, Hamburger hired a young post-doc from the Washington University Medical School, Stanley Cohen, to identify the active fraction from the tumor. Cohen quickly managed to isolate a nucleo-protein fraction that would stimulate neuronal growth significantly, but it was not clear whether the nucleic acid or protein component was the active agent. Using snake venom as a source of a nucleic-acid digesting enzyme (phosphodiesterase), Cohen showed that the protein fraction had the nerve stimulating property. In fact, the snake venom itself turned out to have a thousandfold greater potency for stimulating neuronal growth than the tumor protein. The


system for studying and characterizing the active fraction, which came to be called the nerve growth factor (NGF), was enhanced further by using male mouse salivary glands as a source (which are far easier to obtain than snake venom). Using their system Cohen eventually fully characterized the protein making up NGF.

As the work progressed, Hamburger stepped back from the day-to-day activity, leaving the project in the hands of Levi-Montalcini and Cohen. They were rewarded for their work with receipt of the 1976 Nobel Prize in Physiology or Medicine. Hamburger was not included, a point that disturbed him more than he often let on. His own work admittedly lay in other directions, and he took solace from having started the NGF work and promoted it intellectually and financially during the crucial early years (1934–1954).

The Genetics of Development . In the 1940s and 1950s, while most classically trained embryologists at best paid lip service to the genetics of development, Hamburger’s work with the creeper mutant provided one model for how the problem could be approached. The creeper mutant was of interest because in the heterozygous state, the legs are greatly foreshortened due to retardation of growth during embryogenesis, whereas in the homozygous state the eye buds develop a peculiar abnormality known as coloboma (homozygous embryos usually die around the 72-hour stage). Because a single gene appeared to affect these two very different traits, Hamburger realized the creeper system could be used to dissect apart the ways in genes affect developmental pathways. When he transplanted proto limb- and eye-bud tissue from the creeper (heterozygous) strain to the flank of an embryo of a normal strain, the transplant developed the mutant phenotype, as expected (Hamburger, 1942a). But when he transplanted an eye primordium from a homozygous strain to the eye region of a normal embryo, a perfectly normal eye developed. Hamburger’s analysis suggested that the effect of the creeper mutation on limb and eye growth must be qualitatively different. The effect on limb

growth was direct, that is, the gene must control some process such as division rate of cells making up the limb tissue, thus affecting (in this case retarding) growth. However, the effect of the creeper gene on eye development must be indirect, altering a secondary process such as development of vasculature of the eye region, rather than a defect in the genetic information for the eye itself.

The outcome of this work suggested that experimental embryology could contribute in at least a small way (for example, by direct and indirect action) to an understanding of the ways in which genes function in development. For the future, he felt “the complete story of the mode of gene action must be written jointly by geneticists, embryologists and physiologists” (Hamburger, 1942a, p. 332). But complex, multicellular organisms were difficult to manipulate for studying the genetics of development, as others, such as Boris Ephrussi and George Beadle, working with Drosophila in the 1930s and 1940s, had also discovered. Recognizing the limitations of the creeper fowl work at the time, Hamburger returned to neuroembryology.

The Development of Behavior . Inspired in part by the work of Konrad Lorenz, Hamburger had long been interested in how behavior develops. In the late 1950s and 1960s, at a time when many of his colleagues were thinking about retiring, Hamburger took up a whole new line of experimental work on the neurobiological origin of behavior. Two embryologically-based concepts guided this research: (1) Behavior has an internally guided ontogenesis in the same way as physical organs and systems; and (2) The ontogenesis of behavior and of the structural development of the nervous system are inseparable processes. When he entered this field Hamburger was only dimly aware of the intense debate occurring among developmental psychologists over the issue of the innate or learned quality of even the simplest behavior. This was the period when American behaviorism (stimulated by the work of B. F. Skinner) was in its ascendancy, creating an atmosphere that left little room for ideas about innate factors in the origin of animal behavior. For example, one behaviorist-based theory argued that early movements of the chick head resulted from the embryonic heartbeat, which forced the head up and down repeatedly, leading to adult pecking movements. Recognizing that much of embryogenesis is guided by internal factors, Hamburger decided to investigate the early origin of some simple chick behaviors. The behaviorist view would require, among other things, that the sensory and motor systems in the embryo would develop simultaneously; it would also see embryonic behaviors as coordinated with sensory input and thus nonrandom. Hamburger’s approach was to determine how neuronal development correlated with the development of observable behavior in the chick.

Investigating the timing of development, Hamburger noted that the chick motor system began to develop before the sensory system, starting at the anterior and proceeding to the posterior region of the spinal chord. Motor neuron development also coincided with the appearance, starting at about 3.5 days, of numerous movements of the head and beak and moving progressively to the wings and hind limbs. Hamburger and his students analyzed these movements, cataloguing their frequency, duration, and degree of complexity. The movements were found to be random and uncoordinated (one leg or wing would move, the other not) and cycling through periods of activity and quiescence. As embryogenesis progressed, the frequency and complexity of movements increased, while the periods of quiescence decreased.

The next step was to test the hypothesis of spontaneous (non-stimulus-based) movement by removing sections of the afferent (sensory) system leading from a developing limb (they chose the right leg), and nerve tracts from the brain in 2–2.5 day-old embryos. From the initiation of the experiment until around the tenth day, the activity of the leg was identical in the experimental and control (in which afferent nerves had not been removed) groups. To check these observations, Hamburger and several post-docs monitored the electrophysiological discharge of spinal cord motor neurons, finding their activity coincided in frequency and duration with observed spontaneous motility. These findings showed clearly that motor activity precedes any sensory input, refuting the orthodox behaviorist explanation. These results were met with considerable opposition, especially within the psychological community. However, with a strong empirical basis, supported by numerous other experiments, Hamburger was able to establish, against opposition from psychologists, the notion of spontaneous motor activity as the beginnings of behavior in vertebrates.

One of Hamburger’s most important contributions to the field of embryology was to devise, with Howard Hamilton, a standardized stage series for chick development. A major problem for development of any organism is to have a well-grounded reference system for the stages through which the embryo passes, so that comparisons between experiments can be made at comparable points in the developmental process. The only existing stage series for the chick was a rather loose one drawn up in F. R. Lillie’s 1919 Development of the Chick. Lillie’s series was based on chronology (hours of incubation), a criterion that can be misleading because incubators do not necessarily operate at the same temperature or maintain the same humidity levels, factors that affect growth rate. Hamburger and Hamilton decided early on that what would be most useful would be a stage series based on visible anatomical characteristics. They agreed further that the stages should be chosen on the basis of clear identifiability in external structures, successive stages should be spaced as closely together as possible, and wherever feasible, quantitative measurements such a beak or toe length should be used. Although not as intellectually exciting as some of his other work, according to investigators in the field the Hamburger-Hamilton stage series is likely to be Hamburger’s most long-lasting legacy (Hamburger and Hamilton, 1951).

Teaching and Administration . As both a teacher and administrator Hamburger left an important legacy. Serving as Zoology Department chairman at Washington University for twenty-five years, he acquired an outstanding group of faculty (including a number of women, of whose work in science he was a champion). Always a dedicated teacher, he taught at least one course every semester even while serving as department chairman. Two of those courses deserve special mention. One was a year-long, integrated course he developed and co-taught for many years on comparative anatomy and development, accompanied by two two-hour lab sessions per week. The other was a laboratory course in experimental embryology, in which students repeated many of the classic experiments; for this course Hamburger prepared his widely used Manual of Experimental Embryology, which went through two editions (Hamburger, 1942b; 1960).

Another of Hamburger’s most important educational influences came through his association with the embryology course at the Marine Biological Laboratory in Woods Hole, first as instructor (1936–1941) and then as director of the course (1942–1947).When he took over as director, he converted what had been a traditional, descriptive course into an experimentally-based one, engendering considerable excitement on the part of students. Through this association Hamburger influenced a whole generation of developmental biologists to take up experimental work. It was also through his association with other embryologists at Woods Hole that Hamburger and two other colleagues, Benjamin Willier (Johns Hopkins) and Paul Weiss (University of Chicago) developed the idea of a comprehensive review of the state of developmental biology in the mid-1950s, The Analysis of Development (Willier, Weiss, and Hamburger, 1955). Articles were written by specialists on particular processes (game-togenesis, early cleavage, nuclear-cytoplasmic interactions) and on the development of particular animal groups (Hamburger and Holtfreter, for example, wrote the comprehensive chapter on amphibian development). This book became the most influential compendium of experimental embryology of the mid-twentieth century.

Hamburger was a member of many learned societies and institutions, including the American Society of Zoologists (president, 1955), American Association for the Advancement of Science (vice-president, chairman section F, 1960), the American Society of Naturalists, the Society for Developmental Biology (president, 1950–1951), and the International Society for Cell Biology and for Developmental Biologists. He was elected to the National Academy of Sciences (U.S.) in 1953, and the American Academy of Arts and Sciences (1959). He was an honorary member of Sigma Xi and Phi Beta Kappa. In addition, he was awarded a number of prizes in recognition of his work on neuroembryology: The F. O. Schmitt Medal in Neuroscience (1976), The Ross G. Harrison Prize in Developmental Biology (1981), the Louisa Gross Horwitz Prize in Cell Biology and Developmental Neurobiology (1981), the Ralph Gerard Prize and Medal of the Society for Neuroscience (1985), the Fidia-Georgetown Award in Neuroscience (1987), the National Medal of Science (1989), the Karl Spencer Lashley Award of the American Philosophical Society (1990) and the first Lifetime Achievement Award from the Society of Developmental Biology (1999). He received three honorary degrees: Washington University (1976); the University of Uppsala, Sweden (1984); and the Rockefeller University (1996).

After he closed his laboratory in the mid-1980s, Hamburger devoted his still prodigious energies to historical studies, including the monograph The Heritage of Experimental Embryology (Hamburger, 1988) and numerous articles, the last, in his ninety-ninth year, an introduction to and translation of a portion of Spemann’s autobiography, focusing on his supposed vitalistic tendencies (Hamburger, 1999). Hamburger died in 2001, at the age of one hundred.

Hamburger’s Holistic Philosophy . Hamburger shared with his mentor Spemann and many of his generation an appreciation of biological phenomena in general, and embryology in particular, as dynamic, interconnected, and holistic processes, not reducible simply to chemical and molecular reactions. Unlike Spemann, who had no abiding interest in biochemistry or genetics, Hamburger understood that both were important as complementary ways of understanding the dynamics of development, in particular cellular differentiation. In contrast to the more reductionist philosophy, however, for Hamburger the chemical and molecular basis of ontogenetic changes was the starting point, not the ending point, of investigation. It was necessary to know, but not sufficient to explain development as an interactive and integrated process. He understood clearly that development was not simply a series of mechanical or chemical process, but occurred at a number of organizational levels, from the molecule to the cell, tissue and organ-system.

Hamburger adhered to what might be called (he did not use the term himself) a holistic materialist philosophy. He had no patience with vague or vitalistic ideas, or mystical, immaterial directive forces like the “entelechy” put forward by older biologists such as Hans Driesch. His holistic view was non-mystical and practical. It respected the wholeness, that is, the integrity of the embryo. He once said he made a pact with the embryo: “I promised the embryo that if it would reveal to me some of its secrets I would never homogenize it in a Waring blender.” He then added, “I think we have both kept our promises.”


A complete bibliography of Hamburger’s published writings can be found in his papers at the Woods Hole Marine Biological Laboratory Library, Special Collections, as well as on the Washington University Library’s Internet site, available from; a few of the most important are listed in Hamburger’s autobiographical sketch in History of Neuroscience in Autobiography, edited by L. R. Squire, Vol. 1 (Washington, DC: Society for Neuroscience, pp. 222–250, and in the Oppenheim paper listed below.


Embryological Writings

“The Effects of Wing Bud Extirpation in Chick Embryos on the Development of the Central Nervous System.” Journal of Experimental Zoology 68 (1934): 449–494. The first paper in which Hamburger laid out his three-point concept for how limb bud tissue influenced motor neuron growth; this is the paper that also got Levi-Montalcini to start working on the problem of nerve growth during chick development.

“The Larval Development of Reciprocal Species Hybrids of Triton taeniatus(and Tr. palmatus x Triton cristatus.” Journal of Experimental Zoology 73 (1936): 319–373. One of Hamburger’s first attempts to study the effects of different genetic backgrounds (through interspecific hybridization) on developmental processes.

“Motor and Sensory Hyperplasia Following Limb Bud Transplantations in Chick Embryos.” Physiological Zoology 12 (1939): 268–284.

“Transplantation of Limb Primordia of Homozygous and Heterozygous Chondrodystrophic (“Creeper”) Chick Embryos.” Physiological Zoology 14 (1941): 355–364. In this paper Hamburger showed that limbs from genetically defective embryos (with the “creeper” gene) could develop normally if transplanted to a non-mutant embryo.

“The Developmental Mechanics of Hereditary Abnormalities in the Chick,” Biological Symposia 6 (1942a): 311–334.

A Manual of Experimental Embryology. Chicago: University of Chicago Press, 1942b; revised 1960.

With Rita Levi-Montalcini. “Proliferation, Differentiation, and Degeneration in the Spinal Ganglia of the Chick Embryo under Normal and Experimental Conditions.” Journal of Experimental Zoology 111 (1949): 457–502. This paper reports the first results from the authors’ collaboration, confirming Levi-Montalcini’s observations of neuronal death, and the promotion of the “recruitment” over the “inductive” hypothesis for the effects of limb buds on neuronal growth.

With Rita Levi-Montalcini. “Selective Growth Stimulating Effects of Mouse Sarcoma on the Sensory and Sympathetic Nervous System of the Chick Embryo.” Journal of Experimental Zoology 116 (1951): 321–362.

With Howard Hamilton. “A Series of Normal Stages in the Development of the Chick Embryo.” Journal of Morphology 88 (1951): 49–92.

With Rita Levi-Montalcini. “A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo.” Journal of Experimental Zoology 123 (1953): 233–288.

With Rita Levi-Montalcini and Stanley Cohen. “A Nerve Growth-stimulating Factor Isolated from Sarcomas 37 and 180.” Proceedings of the National Academy of Science USA 40 (1954): 1014–1018.

With Benjamin Willier and Paul Weiss, eds. Analysis of Development. Philadelphia: W. B. Saunders, 1955.

“Some Aspects of the Embryology of Behavior.” Quarterly Review of Biology 38 (1963): 342–365.

With Elizabeth Wenger and Ron Oppenheim. “Motility in the Chick Embryo in the Absence of Sensory Input.” Journal of Experimental Zoology 162 (1966): 133–160.

“The Developmental History of the Motor Neuron.” Neuroscience Research Program Bulletin Supplement 15 (1977): 1–37.

Historical Writings

“Hans Spemann and the Organizer Concept.” Experientia 25 (1969): 1121–1125.

“Hilde Mangold, Co-Discoverer of the Organizer.” Journal of the History of Biology 17 (1984): 1–11.

The Heritage of Experimental Embryology. Oxford: Oxford University Press, 1988. A very useful summary of the development of the Freiburg group and the organizer concept. Interspersed with Hamburger’s personal commentary (in italics). This very concise and information-filled book provides one of the best examinations of the science coming out of the Spemann lab. Hamburger also devotes a whole chapter to the work of his close friend and colleague, Johannes Holtfreter.

“The Ontogeny of Neuroembryology.” Journal of Neuroscience 8 (1988): 3535–3540.

“The History of the Discovery of the Nerve Growth Factor.” Journal of Neurobiology 24 (1993): 893–897.

“Memories of Professor Hans Spemann’s Department of Zoology at the University of Freiburg, 1920–1932.” International Journal of Developmental Biology 40 (1996): 59–62.

Wilhelm Roux: Visionary with a Blind Spot.” Journal of the History of Biology 30 (1997): 229–238.

“Hans Spemann on Vitalism in Biology: Translation of a Portion of Spemann’s Autobiography.” Journal of the History of Biology 32 (1999): 231–243.


Allen, Garland E. “A Pact with the Embryo: Viktor Hamburger, Holistic and Mechanistic Philosophy in the Development of Neuroembryology, 1927–1955.” Journal of the History of Biology 37 (2004): 421–475. Focuses particularly on the philosophical bases of Hamburger’s holistic philosophy and its derivation from Spemann and philosopher Martin Heidegger.

Cowan, W. Maxwell. “Viktor Hamburger’s Contribution to Developmental Neurobiology: An Appreciation.” In Studies in Developmental Neurobiology: Essays in Honor of Viktor Hamburger, edited by W. Maxwell Cowan. New York: Oxford University Press, 1981.

Gluecksohn-Waelsch, Salome. “Viktor Hamburger and Dynamic Concepts of Developmental Genetics.” In Studies in Developmental Neurobiology: Essays in Honor of Viktor Hamburger, edited by W. Maxwell Cowan. New York: Oxford University Press, 1981.

Kirk, David, and Garland E. Allen. “Viktor Hamburger: A Prepared, Persistent and Deserving Mind Favored by Many Fortuities.” Developmental Dynamics 222 (2001): 545–551.

Levi-Montalcini, Rita. “One of Hans Spemann’s Pupils.” In Studies in Developmental Neurobiology: Essays in Honor of Viktor Hamburger, edited by W. Maxwell Cowan. New York: Oxford University Press, 1981.

Lillie, Frank R. The Development of the Chick. New York: Henry Holt, 1919.

Oppenheim, Ronald W. “Viktor Hamburger (1900–2001): Journey of a Neuroembryologist to the End of the Millennium and Beyond.” Neuron 31 (2001): 179–190.

———, and Jean Lauder. “Viktor Hamburger at 100: Eight Decades of Neuroembryological Research, 1920–2000.” International Journal of Developmental Neuroscience 19 (2001): 117–122.

Provine, Robert R. “In the Trenches with Viktor Hamburger and Rita Levi-Montalcini (1965–1974): One Student’s Perspective.” International Journal of Developmental Neuroscience 19 (2001): 143–149.

Garland E. Allen